ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4429A>T (p.Ile1477Phe)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002333943 SCV002628144 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-28 criteria provided, single submitter clinical testing The p.I1477F variant (also known as c.4429A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 4429. The isoleucine at codon 1477 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003094695 SCV003202638 uncertain significance Hereditary breast ovarian cancer syndrome 2023-08-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1477 of the BRCA2 protein (p.Ile1477Phe). This variant is present in population databases (no rsID available, gnomAD 0.006%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 1740524). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions.
University of Washington Department of Laboratory Medicine, University of Washington RCV002333943 SCV003850503 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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